Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Signal transduction initiated by interaction of immune complexes (IC) with Fc gamma RII and Fc gamma RIII receptors on human neutrophils was studied by investigating the capacity of well-defined complexes to stimulate O2- generation in neutrophils. IC consisting of polyclonal rabbit antibody to human albumin were prepared at equivalence (insoluble complexes) and at five times Ag excess (soluble complexes). Stimulation of human neutrophils with soluble and insoluble IC caused a dose-dependent activation of the respiratory burst and O2- generation. Incubation of neutrophils with cytochalasin B significantly enhanced O2- generation in neutrophils stimulated with soluble IC. In contrast, cytochalasin B treatment had a minimal effect on O2- generation in neutrophils stimulated with insoluble IC. Treatment of neutrophils with PGE1 or pertussis toxin (PTx) significantly inhibited O2- generation by soluble IC-stimulated neutrophils. However, neither PGE1 nor PTx treatment significantly altered O2- generation in neutrophils stimulated with insoluble complexes. Although O2- generation induced by soluble IC was significantly inhibited by mAb against both Fc gamma RII and Fc gamma RIII receptor, insoluble IC stimulation of neutrophil O2- generation was significantly diminished only by mAb against Fc gamma RIII receptor. Cross-linking of either Fc gamma RII or Fc gamma RIII receptors on neutrophil surfaces induced O2- generation, and this activation was inhibited by both PGE1 and PTx treatment. These findings indicate that soluble and insoluble ICs induce O2- production in human neutrophils through distinct mechanisms. Soluble IC induce activation of neutrophils through a PTx- and PGE1-sensitive pathway that is dependent upon both Fc gamma RII and Fc gamma RIII receptors. Although insoluble IC induce O2- production through a PTx and PGE1 insensitive pathway mediated primarily through Fc gamma RIII receptor.
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PMID:Soluble and insoluble immune complexes activate human neutrophil NADPH oxidase by distinct Fc gamma receptor-specific mechanisms. 217 May 30

The effects of pertussis toxin (PT) on human neutrophil responses mediated by the 42-kDa IgG Fc R (Fc gamma R42) were compared with its effects on responses mediated by the FMLP receptor. Pre-treatment of neutrophils with PT completely inhibited FMLP stimulation of superoxide production and blocked over 95% of FMLP-stimulated degranulation. PT inhibited superoxide production stimulated by Fc gamma R42 cross-linking by 92%. In contrast, degranulation stimulated by Fc gamma R42 was only partially inhibited, with beta-glucuronidase release inhibited by 54%, lysozyme by 33%, and lactoferrin by 78%. With either stimulus, PT inhibition was maximal in the range from 1.8 to 2 micrograms/ml. Responses to both stimuli declined in a parallel fashion with increasing time of exposure to PT with maximal inhibition occurring after 2 h of exposure. Inhibition of FMLP responses and Fc gamma R42-mediated superoxide production, but not degranulation, correlated with ADP-ribosylation of a 45-kDa membrane protein. Inhibition by PT of Fc gamma R42-mediated responses was not due to a change in receptor number. These data suggest that activation of polymorphonuclear neutrophils via Fc gamma R42 proceeds through two pathways, only one of which is regulated by a PT-sensitive G protein.
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PMID:Pertussis toxin inhibits human neutrophil responses mediated by the 42-kilodalton IgG Fc receptor. 296 66

T lymphocytes of rats treated with Bordetella pertussis vaccine (BP) formed a soluble factor that enhanced the glycosylation of IgE-binding factors during their biosynthesis, and provided the latter factors with the biologic activity to potentiate the IgE response. The present experiments demonstrated that pertussigen (leukocytosis-promoting factor) from BP induced normal rat spleen cells to form the glycosylation-enhancing factor. The same factor was obtained by incubation of normal spleen cells with 5 micrograms/ml, but not 2 micrograms/ml, concanavalin A. When normal rat mesenteric lymph node cells were incubated with the glycosylation-enhancing factor together with IgE, IgE-binding factors formed by the cells selectively potentiated the IgE response. The IgE-binding factors formed by the same cells upon incubation with IgE alone neither enhanced nor suppressed the IgE response. The glycosylation-enhancing factor changed the nature of IgE-binding factors formed by the rat-mouse T cell hybridoma, 23A4. IgE-binding factors induced by IgE alone lacked affinity for lentil lectin, whereas those induced by IgE in the presence of the glycosylation-enhancing factor had affinity for the lectin. The cell source of the glycosylation-enhancing factor appeared to be W 3/25+ Fc gamma R+ T cells. The glycosylation-enhancing factor was protein in nature and had a m.w. of about 25,000. The factor had affinity for acid-treated Sepharose and could be recovered from the beads by elution with lactose. The factor was different from interleukin 2 with respect to both its affinity for galactose and its isoelectric point.
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PMID:Modulation of the biologic activities of IgE-binding factor. II. Physicochemical properties and cell sources of glycosylation-enhancing factor. 660 Nov 39

Leukoclastic vasculitis is thought to be initiated by deposition of immune complexes (ICs) in the vascular wall. To study the neutrophil response in a related in vitro model, we primed human umbilical vein endothelial cell (HUVEC) monolayers with antibodies against human fibronectin. The resulting respiratory burst to the immobilized ICs depended on the antibody concentration used to prime the monolayers and included a marked release of primary and secondary granule constituents. On IC-bearing HUVEC monolayers, but not on ICs directly bound to tissue culture dishes, blocking monoclonal antibodies (mAbs) to crystallizable fragment-gamma receptor II (Fc gamma RII) and Fc gamma RIII markedly inhibited the respiratory burst and the release of elastase. However, on both surfaces the neutrophil response was strongly inhibited by mAbs against CD18. Regardless of whether we used neutrophils from a patient with severe paroxysmal nocturnal hemoglobinuria (PNH) lacking the Fc gamma RIII, or whether the Fc gamma RII-mediated signal transduction was blocked by pertussis toxin, the respiratory burst to the IC-bearing HUVECs was essentially unchanged. With PNH neutrophils, the respiratory burst was predominantly blocked by an anti-Fc gamma RII mAb. In contrast, the response of pertussis toxin treated neutrophils was strongly inhibited by a mAb against Fc gamma RIII. Together these data indicate that the answer of neutrophils to ICs immobilized at the endothelial barrier depends on the cooperative function of both low-affinity Fc gamma Rs.
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PMID:Neutrophil activation in response to immune complex-bearing endothelial cells depends on the functional cooperation of Fc gamma RII (CD32) and Fc gamma RIII (CD16). 749 May 18

Neutrophils express several receptors for the Fc region of IgG molecules. Specific cross-linking of the type II receptor (Fc gamma RII) can be achieved by treating neutrophils with the Fab fragment of a specific monoclonal antibody IV.3 against the receptor followed by goat anti-mouse IgG F(ab')2 fragment. Such treatment initiates a number of neutrophil responses including the release of O2-. and increased protein tyrosine phosphorylation. The increase in tyrosine phosphorylation is rapid and transient and correlates with O2-. release. Both responses are inhibited by pretreatment of neutrophils with a protein tyrosine kinase inhibitor, genistein. The increase in protein tyrosine phosphorylation is not inhibited by pretreatment of neutrophils with pertussis toxin or an intracellular Ca2+ chelator, but is enhanced by a phosphoprotein phosphatase inhibitor, okadaic acid. The activity of a neutrophil Ca2+/calmodulin-dependent protein kinase II (CAMPKII) is also stimulated by cross-linking Fc gamma RII. The increase in CAMPKII activity is inhibited by pretreatment with either genistein or Ca2+ chelator. The results suggest that the increase in protein tyrosine phosphorylation induced by cross-linking of Fc gamma RII requires neither pertussis-toxin-sensitive G-proteins nor a rise in intracellular Ca2+ but can be regulated by protein phosphatases. Furthermore, protein tyrosine phosphorylation may be an early signal functionally linked to Fc gamma RII-mediated signal transduction leading to CAMPKII activation and O2-. release in human neutrophils.
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PMID:Tyrosine phosphorylation induced by cross-linking of Fc gamma-receptor type II in human neutrophils. 753 66

Digital fluorescence calcium imaging was used to investigate and identify the primary biological responses of human neutrophils to monomeric immunoglobulin E (IgE). Treatment of neutrophils with IgE caused a transient rise in the level of intracellular calcium that was inhibited by pertussis toxin. The calcium rise was due mainly to release from an intracellular membrane-enclosed store that is also sensitive to the chemotactic peptide formyl-Met-Leu-Phe. The IgE-induced calcium transient was independent of Fc gamma receptors and of Fc epsilon receptor ligation. Our data suggest that the mere binding of IgE to neutrophils is sufficient to evoke a biological response without the need for IgE/receptor cross-linking.
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PMID:Monomeric human IgE evokes a transient calcium rise in individual human neutrophils. 756 23

Two tyrosine kinase-dependent pathways exist for activation of the respiratory burst by polymorphonuclear leukocyte (PMN) immunoglobulin G Fc receptors. Direct ligation of Fc gamma RII activates the respiratory burst, but ligation of the glycan phosphoinositol-linked Fc gamma RIIIB does not. Instead, this receptor and the integrin complement receptor CR3 synergize in activation of the respiratory burst (Zhou, M.-J., and Brown, E. J. (1994) J. Cell Biol. 125, 1407-1416). Here we show that direct ligation of Fc gamma RII leads to activation and Triton X-100 insolubility of the Src family kinase Fgr, without effect on the related myeloid Src family member Hck. In contrast, adhesion of PMN via Fc gamma RIIIB leads to activation and Triton X-100 insolubility of Hck but not Fgr. The exclusive association of Fc gamma RIIIB with Hck activation and Triton insolubility is not solely a result of its glycan phosphoinositol anchor, since decay accelerating factor (CD55), another prominent glycan phosphoinositol-anchored PMN protein, is associated with Fgr insolubility to a greater extent than Hck. Ligation of decay accelerating factor, with or without coligation of CR3, does not activate the PMN respiratory burst. Coligation of Fc gamma RIIIB with Fc gamma RII overcomes the pertussis toxin inhibition of H2O2 production in response to direct ligation of Fc gamma RII. These data support the hypothesis that activation of Hck upon Fc gamma RIIIB ligation has a role in generation of the synergistic respiratory burst.
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PMID:Distinct tyrosine kinase activation and Triton X-100 insolubility upon Fc gamma RII or Fc gamma RIIIB ligation in human polymorphonuclear leukocytes. Implications for immune complex activation of the respiratory burst. 776 58

Altered polymorphonuclear leukocyte (PMN) function is thought to contribute to organ dysfunction during the systemic inflammatory response syndrome (SIRS). To test this hypothesis, we evaluated whole blood PMN function adherent to fibronectin or laminin in patients with mild or severe acute pancreatitis as a paradigm for sirs. Whole-blood PMN intracellular H2O2 production, expression of CD32w (Fc gamma R II), CD16 (Fc gamma R III), and phagocytosis were performed using dichlorofluorescein diacetate, fluorescein isothiocyanate-labeled anti-CD32w, CD16, and serum-opsonized fluorescent microspheres. Group I (n x 7) represents normal control individuals; group II (n x 11) represents patients with mild acute pancreatitis. Group III (n x 15) represents critically ill patients with severe acute pancreatitis. Adherence of PMN from groups I and II to matrix proteins resulted in a 5% to 20% increase in each PMN function assayed whereas adherence of PMN from group III to matrix proteins resulted in 50% to 75% increases in each PMN function assayed. Pertussis toxin, pentoxifylline, and dibutyryl cyclic adenosine monophosphate (cAMP) each reduced group I-II H2O2 production and phagocytosis. Pentoxifylline and dibutyryl cAMP but not pertussis toxin reduced group III H2O2 production. Both intracellular H2O2 and phagocytosis assays from group III but not groups I-II showed exaggerated upregulation when exposed to NaF (4 mmol/L). Anti-interleukin-6 reduced the increase in intracellular H2O2 production in group III patients and significantly altered the exaggerated oxidative response to NaF. Longitudinal studies of group III whole-blood PMN showed persistent upregulation of intracellular H2O2 production in those patients whose hospital courses were complicated by multiple system organ failure. These results demonstrate abnormal whole blood PMN function during the systemic inflammatory response syndrome in the presence of fibronectin, or laminin and that this is mediated in part via a pertussis toxin insensitive altered guanosine triphosphate-binding protein.
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PMID:Polymorphonuclear leukocyte dysregulation during the systemic inflammatory response syndrome. 811 41

Previous studies have shown that intracellular killing of bacteria by monocytes is stimulated by interaction between IgG and Fc gamma receptors (Fc gamma R) in the membrane of these cells. In the present study anti-Fc gamma R monoclonal antibodies (mAb) were used to investigate the relative contributions of the various classes of Fc gamma R to the intracellular killing of Staphylococcus aureus by human monocytes and the biochemical pathways involved. Anti-Fc gamma RI or anti-Fc gamma RII mAb, but not anti-Fc gamma RIII mAb, efficiently stimulated the intracellular killing of bacteria by monocytes. Cross-linking Fc gamma RI or Fc gamma RII, but not Fc gamma RIII, on monocytes with mouse anti-Fc gamma R mAb followed by bridging with F(ab')2 fragments of goat anti-mouse IgG enhanced this process. Since the NADPH oxidase inhibitor diphenyleneiodonium blocked the Fc gamma R-mediated intracellular killing of S. aureus, oxygen-dependent bactericidal mechanisms are most probably involved. Cross-linking Fc gamma RI or Fc gamma RII but not binding of the mAb to the Fc gamma R on monocytes activated phospholipase C, as demonstrated by the increase in the intracellular concentration of inositol-(1,4,5)-triphosphate. The enhanced intracellular killing stimulated by cross-linking Fc gamma R on monocytes was completely blocked by U-73122, an inhibitor of phospholipase C-dependent processes. Protein kinase C activity, but not the rise in the cytosolic free Ca++ concentration or pertussis toxin-sensitive G proteins, is essential for the Fc gamma R-mediated intracellular killing of bacteria by monocytes. Together, these results demonstrate that cross-linking Fc gamma RI or Fc gamma RII is equally effective in stimulating the intracellular killing of bacteria by monocytes and that this stimulation is a phospholipase C-dependent process.
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PMID:Stimulation of the intracellular killing of Staphylococcus aureus by human monocytes mediated by Fc gamma receptors I and II. 822 59

The low affinity IgE receptor CD23 may play a role in several B lymphocyte functions, such as cell activation and multiplication, Ag presentation, and IgE production. We have previously reported that ligation of the CD23 molecule with anti-CD23 mAb, or IgE-anti-IgE complexes, leads to phosphoinositide hydrolysis and calcium mobilization through the generation of Inositol (1,4,5) trisphosphate via a process involving a Pertussis toxin insensitive GTP-binding protein. In our work, we show that anti-CD23 mAb elicit an increase in cAMP concentration in human peripheral blood-derived B lymphocytes. This effect was detected both in resting and in IL-4-stimulated B cells displaying, respectively, low and high levels of CD23. Maximum cAMP accumulation was reached about 20 min after addition of the mAb. Involvement of Fc gamma RII in this process could be excluded because cAMP increase was also triggered by mAb anti-CD23 F(ab')2 fragments. Accumulation of cAMP was also observed when IgE-sensitized activated B lymphocytes were challenged with the specific hapten. Several lines of evidence indicate that the cAMP increase after CD23 ligation may result, in part, from the stimulation of phosphoinositidase C, inasmuch as it was markedly impaired by treatment with TMB-8, an inhibitor of InsP3-induced calcium release from intracytoplasmic stores and with BAPTA, an intracellular calcium chelator. Addition of GTP-gamma S to permeabilized B cells or to membrane preparations did not potentiate the effect of the mAb, suggesting that a Gs protein is not directly implicated in the generation of cAMP. Besides, cAMP accumulation is not due to the production of PG because it is not modified by indomethacin, an inhibitor of the cyclooxygenase pathway. Pretreatment of B lymphocytes with either anti-CD23 mAb or IL-4 led to autologous as well as heterologous desensitization. This negative cross-talk, at the level of cAMP, between the signaling pathways triggered by ligation of CD23 and of the IL-4 receptor, could contribute to the inhibitory effect of anti-CD23 mAb on IL-4-dependent B cell activation and differentiation.
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PMID:Ligation of CD23 triggers cyclic AMP generation in human B lymphocytes. 838 20


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